Interleukin-1 refers to a family of molecules secreted by stimulated macrophages which effectuate multiple biological responses. The activities of interleukin-1 are summarized in Murphy, British Journal of Rheumatology, 24(suppl 1) 6-9, (1985), and Oppenheim et al., Immunology Today, 2, 45-55 (1986).
Interleukin-1 has been described to mediate T-lymphocyte proliferation and the acute phase response in inflammation. It also demonstrates pyrogenic and proinflammatory effects. Interleukin-1 induces connective tissue changes, and has been demonstrated to induce the release of degradative enzymes from mesenchymal cells that are present at the sites of bony erosion in inflammatory disease states such as rheumatoid arthritis. Billingham, Brit. J. Rheumatology, 24 (suppl 1), 25-28, (1985). Dayer, Brit. J. Rheumatology, 24 (suppl 1), 15-20, (1985). The production of acute phase proteins in hepatocytes during the acute phase of inflammation is mediated by IL-1. Whicher, Brit. J. Rheumatology, 24 (suppl 1), 21-24, (1985).
Interleukin-1 is also involved as a mediator in the inflammatory skin disease, psoriasis. Camp, et al., J. Immunology, 137, 3469-3474, (1986), and Ristwo, Proc. Natl. Acad. Sci., USA 84, 1940-1944, (1987). It is cytotoxic for insulin producing beta cells in the pancreas, and is thus a causative factor in the development of some forms of diabetes mellitus. Bendtzen, et al., Science, 232, 1545-1547, (1986), and Marx, Science, 239, 257-258, (1988). Interleukin-1 also appears to be involved in the development of atherosclerotic lesions or atherosclerotic plaque. Marx, Science, 239, 2557-258, (1988). Interleukin-1 stimulates growth and proliferation of vascular smooth muscle cells, an effect which is greater in the absence or suppression of endogenous prostaglandins, which could lead to thickening of vascular walls such as occurs in atherogenesis. Libby, et al, J. Clin. Invest., 81, 487-498, (1988).
It is therefore advantageous to control the release of interleukin-1 and interleukin-1-mediated conditions such as inflammation, psoriasis, diabetes, and atherosclerosis. Also, a need exists to control or treat interleukin-1 mediated inflammation without production of concomitant side effects which presently accompany the use of antiinflammatory steroids and non-steroidal antiinflammatory agents.